A process for large-scale batch or continuous production of polyphenols using enzyme- mediated reactions where the reactions are carried out in 1) bulk solvents, 2) reversed micelles, or 3) a biphasic system. The process incorporates methods for recycling non-consumed reactants back into the system and controlling reaction conditions such that high product yields, control of molecular weight, and polydispersity are obtained.
Phenolic resins such as novolacs and resoles are commercially produced by condensing phenol and formaldehyde at various molar ratios in the presence of acid or base catalysts. However, the confirmed carcinogenic nature of formaldehyde poses a major threat to personnel involved in polyphenol production in industry and to the end user. Residual amount of formaldehyde in the finished product is unavoidable and undesirable.
Alternatively, inorganic catalysts or biocatalysts can be used to produce polyphenols without the need for formaldehyde. Enzymatically synthesized polyphenols may find applications in coatings, laminates, wood composites, color developers, and recording materials. Such materials could be cast into thin films or fabric coatings. The polymers can also be tailored for applications in the detergent industry. In addition, polyphenols may be used in photolithography, rechargeable lightweight batteries, and electromagnetic shielding. Enzymatic polymerization of phenols and aromatic amines in mixtures of water-miscible solvents and water was first reported by Klibanov and co-workers, (J. S. Dordick, M. A. Marlett, A. M. Klibanov, Biotechnol. Bioeng. 1987, 30, 31-36.) and Pokora and Cyrus, (A. R. Pokora, W. L. Cyrus, U.S. Pat. No. 4,647,952, 1987, Mead Corporation., U.S.A.).
There are numerous advantages to using enzymes to catalyze phenol polymerization including mild reaction conditions, fast reaction rates, high substrate specificity and minimal by-product formation. Polymers produced by enzymatic reactions have the additional advantage of having extensive backbone conjugation leading to electronic and electro optic applications. Horseradish peroxidase (HRP) is the most commonly used enzyme for these polymerization reactions carried out in solvent/water mixtures and microemulsions.
Dordick et al., Vol. # 30,1987 Biotechnol. Bioeng. 31-36, used HRP in a dioxane/water system to prepare a number of polymers and copolymers from various phenolic monomers. Akkara et al., 29 J. Polym. Sci. A 1561 (1991), prepared polymers and copolymers of various phenols and aromatic amines using these same reactions and carried out detailed characterization of the polymer products. Para-alkylphenols were also polymerized at oil-water (reversed micelles) and air-water (Langmuir-Blodgett trough) interfaces. Because of their amphophilic nature, the alkylphenols are partitioned at the interface, and in the presence of HRP and hydrogen peroxide the monomers are oxidatively coupled to form polymers. The poly(para-alkylphenols) prepared in reverse micelles were shown to exhibit relatively more uniform molecular weight distribution than those prepared in bulk organic solvents.
However, earlier attempts to control the polymer molecular weight and molecular weight distribution by varying the time of reaction or hydrogen peroxide concentration were unsuccessful in both reversed micelles and bulk solvents. Initial hydrogen peroxide concentration was found to be stoichiometrically proportional to the monomer conversion, a hallmark of stepwise polymerization and a phenomenon observed previously, and there was no effect on the polymer molecular weight and polydispersity.
The polymers can be modified by adding functional groups to the polymeric backbone, significantly enhancing the utility of these polymers. xe2x80x9cFunctionalizationxe2x80x9d enables the polymers to be used to treat fabrics, to form selectively permeable membranes, and to improve the performance of integrated circuit chips, among other applications.
Palmitoyl chloride may be added to the polymer to make the polymer easily processable, e.g., as coatings, films, or finishes. Cinnamoyl chloride may be added to create controlled pore size membranes (e.g., xe2x80x9cmolecular sievesxe2x80x9d) or to enhance the polymers"" ability to absorb UV radiation (e.g. photolithography, sunglasses, etc.). In their latter use, the modified polymers are applied to a silicon substrate as an undercoating (under non-functionalized polyphenols or polyaromatic amines that are then applied as a spin coating) in an IC chip to control the precision of UV etching, by inhibiting UV scattering, of circuitry into the spin-coated polymer layer. In addition, these cinnamoyl chloride-modified polymers are very thermostable, which allows their use in a variety of applications where heat is ordinarily a problem. In addition, photosensitive functional groups may be added to enhance the utility of the polymers in other applications.
The polymers also may be modified to create active matrices and systems allowing the controlled-release of materials, such as drugs, insecticides, and fertilizers. If biotin or other ligands are added to the polymer chain, the polymer can be used as chromatography packing, which may be used to separate and purify proteins.
Despite the study of how the functionality of the polymers varies depending upon whether, and with what, the molecules are modified, it has not been shown that the molecular weight and the molecular weight distribution (i.e. xe2x80x9cpolydispersityxe2x80x9d) of polyphenols and polyaromatic amines also can significantly influence the functional properties of the polymers.
Although the reactions employed by the invention are known in the industry, processes have not been developed for large-scale production of phenolic or aromatic amine polymers in enzyme-mediated reactions from which non-consumed reactants are recycled This invention relates to such a process for large-scale production of phenolic or aromatic amine polymers in enzyme-mediated reactions from which non-consumed reactants are recycled. The process specifically relates to recycling the solvent to minimize waste and lower processing costs.
It is therefore an object of this invention to provide a low cost process for large-scale production of polyphenols or polyaromatic amines using enzyme-mediated reactions from which non-consumed reactants are recycled back into the reaction system.
More particularly it is an object of this process to provide a closed system to recycle the solvent back into the reaction system to minimize waste and to lower processing costs.
It is a further object of this invention to provide a method for producing polyphenols or polyaromatic amines which incorporates methods for recycling non-consumed reactants and non-consumed reaction medium back into the system and for controlling reaction conditions such that high product yields, low molecular weight, and low polydispersity are obtained.
The process generally includes polymerizing a monomer in a reactor with various pre-reaction components, wherein polymerization is catalyzed by an enzyme, yielding phenolic or aromatic amine polymers, non-consumed reactants and reaction medium, wherein the non-consumed reactants and reaction medium form post-reaction components; isolating the polymers from the post-reaction components and recycling at least a portion of the post-reaction components back into a mixing unit.
The reactants comprise monomers, enzyme, and hydrogen peroxide. The reaction medium may be a reversed micellar solution comprising water, a solvent and a surfactant. The reaction medium may alternatively include water and a water-miscible solvent in a monophasic system. Additionally, in a biphasic system the reaction medium may comprise a first phase, where the first phase comprises water, and a second phase, where the second phase comprises a water-immiscible solvent. In this latter embodiment the reactor may comprise a stirred tank to create a dynamic emulsion.
After polymerization, the polymer may be isolated from the reaction components by means of a filtration unit yielding isolated polymers and a filtrate, where the filtrate includes the non-consumed reactants and the reaction medium.
After isolating the polymer, the recycling step may include the following steps.
(A) In a monophasic solvent system by: 1) isolating a sample of the filtrate; 2) analyzing the sample by means of a monitoring device to determine concentration of the nonconsumed reactants and volume of the reaction medium, together comprising post-reaction components; 3) recycling the non-consumed reactants and reaction medium back into the system; 4) communicating the concentration and the volume levels for the post-reaction components to all flow controllers; and 5) introducing the calculated amounts of each reactant and reaction medium into the reactor by means of controlling the respective flow rate.
(B) In a reversed micellar solution by: 1) isolating a sample of the filtrate by means of a sampling port; 2) analyzing the sample by an analyzing means to determine the concentrations of nonconsumed reactants, surfactant and water and volume of the reaction medium, together the post-reaction components; 3) recycling the post-reaction components to a mixing unit via a feedback controller; 4) communicating the calculated concentrations and volume information from the feed back controller to the respective flow controllers; 5) introducing the calculated amounts of the reactants, surfactant, water and solvent into their respective mixing ports/units; 6) introducing the solution into the reactor; and 7) initiating the polymerization reaction by adding the calculated amount of hydrogen peroxide at a predetermined rate.
(C) In an immobilized system by: 1) analyzing the filtrate for nonconsumed reactants; and 2) returning the filtrate to the top of the bed after adding the calculated amounts of reactants and solvent.